This proposal describes the capacity of the University of Oklahoma Health Sciences Center and the University of Texas Southwestern Medical Center at Dallas to support a Core Clinical Center for the Transfusion Medicine/Hemostasis Clinical Research Network. Key personnel have expertise in hemostasis, transfusion medicine, protocol design, Clinical trial execution, and data analysis. Programs for mentoring trainees and junior faculty are described. Protocols are proposed that address important unresolved issues in hemostasis. Protocol 1: Initial management of patients with thrombotic thrombocytopenic purpura (TTP): plasma exchange treatment (standard therapy) compared to plasma exchange treatment plus high-dose glucocorticoid. Plasma exchange treatment has proven efficacy for TTP, however some patients have multiple exacerbations and require prolonged treatment. Glucocorticoids are of unproven efficacy, possibly because previously reported patients have heterogeneous etiologies. Recent observations that autoantibodies to von Willebrand factor-cleaving protease are the etiology for TTP in many patients provide a rationale for immunosuppressive treatment. It is hypothesized that high-dose glucocorticoid (methylprednisolone, 1,000 mg for 3 days followed by prednisone, 1 mg/kg/day) will improve clinical outcomes. Superior outcomes with glucocorticoid treatment would suggest further investigation of immunosuppressive regimens. Protocol 2: Initial management of children with idiopathic thrombocytopenic purpura (ITP): anti-D (standard therapy) compared to observation. The most controversial topic addressed by the American Society of Hematology (ASH) ITP Practice Guideline was the initial management of childhood ITP. The majority opinion of the ASH panel favored drug treatment over observation, consistent with recent surveys of the American Society of Pediatric Hematology/Oncology. However guidelines by the British Paedriatric Haematology Group recommend observation alone as appropriate initial management. Randomized clinical trials have demonstrated that the platelet count recovers more rapidly with treatment, but no studies have described the effect of drug treatment on clinical outcomes of bleeding and quality-of life. It is postulated that new episodes of severe bleeding will be equivalent between children treated with anti-D or managed by observation alone, and that the quality-of-life of children and their parents will be better when managed with observation alone. Equivalent clinical outcomes would support the practice of avoiding expensive treatment with potential harms and limited world-wide availability.